Insulin-like growth factor (IGF)-I and IGF binding protein-3 concentrations in fluid from human stimulated follicles

Insulin-like growth factor-I (IGF-I) and IGF binding protein-3 (IGFBP- 3) play an important role in regulating follicle growth and maturation. We have evaluated whether responsiveness to gonadotrophins during an in- vitro fertilization (IVF) treatment is related to follicular fluid IGF- I and IGFBP-3 concentrations. We also investigated if a difference is present in IGF-I and IGFBP-3 concentrations between patients treated with human menopausal gonadotrophin (HMG) and patients treated with highly purified follicle stimulating hormone (FSH). We have measured IGF-I and IGFBP-3 in follicular fluid from pre-ovulatory follicles in an IVF programme. All 70 patients were stimulated after being down- regulated with a gonadotrophin-releasing hormone (GnRH) analogue. IGF-I concentrations in follicular fluid were significantly inversely correlated with the number of ampoules FSH administered and number of days of FSH administration, and significantly correlated with the number of follicles aspirated. IGFBP-3 concentrations were not correlated with any other parameter measured nor were IGF-I and IGFBP-3 concentrations correlated. IGFBP-3 concentrations were significantly higher in patients receiving highly purified FSH compared with patients receiving HMG (P < 0.005). These results are new evidence that IGF-I concentration in follicular fluid is higher in women who respond better to follicular stimulation, i.e. women who grow many follicles, women who need a shorter duration of stimulation and women who need fewer ampoules FSH before oocyte retrieval.      

Signal transduction modulation by lithium: cell culture, cerebral microdialysis and human studies.

Considerable evidence suggests that signal transduction pathways are targets of lithium (Li) action. A number of investigators have reported that Li attenuates both adenylate cyclase (AC) activity and phosphoinositide (PI) turnover in rodents and in humans, thus "dampening" these systems. We have studied selected components of these second-messenger systems in a series of clinical and preclinical investigations. To overcome confounding effects of alterations in mood state, we examined AC activity and G-protein ribosylation in peripheral blood cells from 10 healthy volunteers, prior to and following 14 days of Li administration. Basal and postreceptor [cesium fluoride (CsF) or Gpp(NH)p] stimulated AC activity were unaffected in lymphocytes. In contrast, both basal and stimulated AC activity in platelets were significantly augmented, compatible with an attenuation of Gi function. Ribosylation of platelet Gs by cholera toxin was unchanged, whereas that of Gi by pertussis toxin (PT) was increased. Given that undissociated G protein is the preferred substrate for PT, our results suggest that Li interferes with subunit dissociation and the subsequent activation of Gi. To determine if Li has similar effects on Gi in the central nervous system, we measured extracellular (EC) cyclic adenosine monophosphate (cAMP) in rat brain by in vivo microdialysis, revealing a dose-dependent increase in cAMP by norepinephrine (NE) antagonized by propranolol. Chronic (4-week) Li doubled basal EC cAMP, while decreasing the fractional response to 100 microM NE. Thus, using in vivo microdialysis, we observed the reported reduction in NE-stimulated AC activity, but only as a function of elevated basal cAMP. Increased basal AC activity has been observed following chronic Li in both humans and rat tissues but generally has not been considered relevant. The PI generating system is another proposed major target for Li that we have studied using an in vitro cell culture model of peripheral blood cells. Chronic (6-day) exposure of neutrophil-like HL60 cells to 1 mM LiCl did not affect agonist fMet-Leu-Phe (fMLP) induced PI turnover. In contrast, Li attenuated both agonist and phorbol ester stimulated Na+/H+ exchange, suggesting reduced protein kinase C (PKC) function. Western blot analysis revealed altered levels of PKC in both membrane and cytosolic fractions. The functional consequences of these complex effects on the two major signal transduction pathways and their interactions in the intact living organism remain to be elucidated.     

Outward currents influencing bursting dynamics in guinea pig trigeminal motoneurons

To initiate and maintain bursts (and plateau potentials) in the presence of serotonin, guinea pig trigeminal motoneurons utilize L-type Ca2+ and persistent Na+ inward currents. However, the intrinsic currents that contribute to burst termination and determine the duration of the interburst interval are unknown. Therefore we investigated the roles of outward currents, whose slow activation is coupled to cytosolic cation (Ca2+ and Na+) accumulation. First we examined a Ca2+-dependent K+ current (IK-Ca) with apamin and Ba2+-substituted, low-Ca2+ solution. Blockade of IK-Ca lengthened burst duration and cycle time but did not abolish bursting. Next we studied the Na+/K+-ATPase pump current (Ip) with cardiac glycosides. In the presence of apamin or low-Ca2+/Ba2+ solution, blocking Ip (with ouabain or strophanthidin) decreased both burst duration and cycle time and ultimately transformed bursting into tonic spiking. We conclude that IK-Ca and Ip contribute to burst termination in trigeminal motoneurons. These currents influence temporal bursting properties such as burst duration and cycle time and may help determine the phasic activity of motoneurons during rhythmic oral-motor behaviors.     

Synthesis and properties of poly(ether imide)s derived from 4,4′-(1,5-naphthylenedioxy)diphthalic anhydride and various aromatic diamines

A naphthalene unit-containing bis(ether anhydride), 4,4′-(1,5-naphthylenedioxy)-diphthalic anhydride, was prepared in three steps starting from the nucleophilic nitro-displacement reaction of 1,5-dihydroxynaphthalene and 4-nitrophthalonitrile in N,N-dimethylformamide (DMF) solution in the presence of potassium carbonate. High-molarmass aromatic poly(ether imide)s were synthesized using a two-stage polymerization process from the bis(ether anhydride) and ten aromatic diamines. The intermediate poly(ether amic acid)s had inherent viscosities of 0,66–1,27 dL/g. The films of poly(ether imide)s derived from some diamines, such as p-phenylenediamine, benzidine, and bis[4-(4-aminophenoxy)phenyl] ether, crystallized and embrittled during the thermal imidization process. The other poly(ether imide)s were amorphous materials and could be fabricated into transparent, flexible, and tough films. These poly(ether imide) films had yield strengths of 111–125 MPa, tensile strengths of 96–150 MPa, elongations to break of 10–38%, and initial moduli of 1,6–2,4 GPa. All of these polymers were insoluble in organic solvents, except for that derived from 2,2-bis[(4-aminophenoxy)phenyl]propane. Their T_g's were recorded in the range of 226–265°C by DSC. Thermogravimetric analysis (TG) showed that all the polymers were stable up to 535°C in both air and nitrogen atmosphere.     

Synthesis and properties of polyamides and poly(amideimide)s based on 4,4′-[1,4(or 1,3)-phenylenebis(isopropylidene-1,4-phenyleneoxy)]dianiline

The diamines 4,4′-[1,4(or 1,3)-phenylenebis(isopropylidene-1,4-phenyleneoxy)]dianiline (p- 3 and m- 3 ) were synthesized in two steps from the condensation of 4,4′-[1,4(or 1,3)-phenylenediisopropylidene]diphenol (p- 1 and m- 1 ) and p-chloronitrobenzene in the presence of K₂CO₃ in N,N-dimethylformamide (DMF), giving the corresponding bis(4-nitrophenoxy) compounds, followed by reduction with the hydrazine/Pd-C system. A series of aromatic polyamides, aliphatic-aromatic polyamides, and poly(amide-imide)s were prepared by the direct polycondensation of the diamines with aromatic or aliphatic dicarboxylic acids and phthalimide unit-bearing dicarboxylic acids in N-methyl-2-pyrrolidone (NMP) using triphenyl phosphite and pyridine as condensing agents. In addition, two series of polyamides were prepared from terephthalic acid or isophthalic acid and aromatic diamines with isopropylidene and/or ether linking groups between the phenylene units, and the structure-property relationships of these polyamides were studied. Almost all the resultant polymers were amorphous in nature and could be solution-cast into transparent, tough, and flexible films. Most of the polymers exhibited moderately high thermal stability. Thus, they are considered as new candidates for processable high-performance polymeric materials.     

New poly(amide-imide) syntheses, 4 Poly(amide-imide)s derived from 2,5-bis(4-aminophenyl)-3,4-diphenylthiophene and various bis(trimellitimide)s

Fifteen bis(trimellitimide)s 2a–o were prepared by condensation of the corresponding aliphatic or aromatic diamines with trimellitic anhydride. A series of structurally new poly(amideimide)s were synthesized by the direct polycondensation of these bis(strimellitimide)s with 2,5-bis(4-aminophenyl)-3,4-diphenylthiophene using triphenyl phosphite and pyridine as condensing agents in N-methyl-2-pyrrolidone (NMP). The resultant poly(amide-imide)s have inherent viscosities in the range between 0,72 and 2,73 dL/g at 30°C in N,N-dimethylacetamide (cf. Tab. 2). The polymers are amorphous and readily soluble in polar aprotic solvents such as N,N-dimethylacetamide (DMAc) and NMP. Transparent and tough films can be cast from their solutions. Most aliphatic-aromatic poly(amide-imide)s show a glass transition in the range between 203 and 242°C in their differential scanning calorimetry (DSC) traces, whereas the wholly aromatic poly(amide-imide)s show no discernible transition before decomposition. The thermal stability of the polymers was evaluated by thermogravimetry which showed the 10% weight-loss temperatures in the range between 414 and 459°C in air and between 451 and 578°C in a nitrogen atmosphere for the aliphatic-aromatic poly(amide-imide)s and above 500°C in both air and nitrogen atmosphere for the wholly aromatic poly(amide-imide)s.     

The effects of face spatial frequencies on cortical processing revealed by magnetoencephalography

To study the spatial frequency (SF) effects on cortical face processing, we recorded magnetoencephalographic responses in seven healthy subjects to upright and inverted human faces. Four face types were used, including original (broad-band SF, BSF), low SF (LSF, <5 cycles/face), middle SF (MSF, 5-15 cycles/face), and high SF (HSF, >15 cycles/face) face images. Using equivalent current dipole (ECD) modeling, neuromagnetic M170 responses peaking around 160-185 ms were localized in right occipitotemporal region across subjects to BSF faces. M170 responses to LSF faces showed longer latency and smaller amplitude compared with those to BSF faces. We found no significant difference between BSF, MSF, and HSF conditions in M170 amplitude or latency. ECD locations for the four upright face conditions were close to one another, although the mean locations for MSF or HSF seemed more medial than those for BSF or LSF. Longer latencies for inverted than upright faces were observed in BSF (183.4+/-8.5 ms versus 168+/-6.9 ms, P<0.001) and LSF face conditions (223.6+/-13.1 ms versus 207.3+/-16.3 ms, P<0.01). M170 ECDs were located more medial for inverted than upright images in either BSF or LSF condition. In conclusion, the less M170 activation to LSF faces suggests that face parts information is important for early face processing. The cortical representations in right occipitotemporal region for configural and face feature processing are overlapping. Our findings on the face inversion effect suggest that inverted BSF and LSF faces may be processed as objects.     

Rapid calculation of detectability in Bayesian single photon emission computed tomography

We consider the calculation of lesion detectability using a mathematical model observer, the channelized Hotelling observer (CHO), in a signal-known-exactly/background-known-exactly detection task for single photon emission computed tomography (SPECT). We focus on SPECT images reconstructed with Bayesian maximum a posteriori methods. While model observers are designed to replace time-consuming studies using human observers, the calculation of CHO detectability is usually accomplished using a large number of sample images, which is still time consuming. We develop theoretical expressions for a measure of detectability, the signal-to-noise-ratio (SNR) of a CHO observer, that can be very rapidly evaluated. Key to our expressions are approximations to the reconstructed image covariance. In these approximations, we use methods developed in the PET literature, but modify them to reflect the different nature of attenuation and distance-dependent blur in SPECT. We validate our expressions with Monte Carlo methods. We show that reasonably accurate estimates of the SNR can be obtained at a computational expense equivalent to approximately two projection operations, and that evaluating SNR for subsequent lesion locations requires negligible additional computation.     

High performance aromatic polyimide fibers, 3. A polyimide synthesized from 3,3′,4,4′-biphenyltetracarboxylic dianhydride and 2,2′-dimethyl-4,4′-diaminobiphenyl

A new high molecular weight aromatic polyimide has been synthesized from 3,3′,4,4′-biphenyltetracarboxylic dianhydride (BPDA) and 2,2′-dimethyl-4,4′-diaminobiphenyl (DMB) in p-chlorophenol at elevated temperature. BPDA-DMB fibers have been spun by a dry-jet wet spinning method. The fibers were elongated and annealed at elevated temperatures above 400°C to achieve excellent mechanical properties. In seven times drawn fibers, the BPDA-DMB molecule packs into a triclinic unit cell with dimensions of a = 2,10(2) nm, b = 1,523(8) nm, c = 4,12(7) nm, α = 61,2(6)°, β = 50,7(7)°, and γ = 78,9(6)° with the number of chain repeating units per unit cell (Z) is sixteen. After annealing at elevated temperatures, the fibers produce a small modification of the unit cell [a = 2,048(6) nm, b = 1,529(5) nm, c = 4,00(2) nm, α = 62,1(3)°, β = 52,2(3)° and γ = 79,6(3)°]. By increasing the draw ratio, both the crystallinity and crystal orientation increase. The BPDA-DMB fibers possess a decomposition temperature of 530°C in nitrogen and 500°C in air at a 5% weight loss when the heating rate is 10°C/min. After extensive drawing, BPDA-DMB fibers exhibit a tensile strength of 3,3 GPa and a tensile modulus of over 130 GPa. Dynamic mechanical behavior of the fibers show both α (glass transition) and β (sub-glass transition) relaxations above room temperature. The nature of the sub-glass transition behavior is described as a noncooperative motion attributed to the diamine portion of the molecule. The activation energy for this relaxation in as-spun fibers is 109 kJ/mol and increases to 144 kJ/mol by increasing the draw ratio. This β relaxation is found to be crystallinity dependent. The α transition is also suppressed by crystallinity which increases with draw ratio.     

Screening of nine SLC25A13 mutations: their frequency in patients with citrin deficiency and high carrier rates in Asian populations

Deficiency of citrin encoded by SLC25A13 causes adult-onset type II citrullinemia (CTLN2) and idiopathic neonatal hepatitis (NICCD). So far we have diagnosed 126 (3) CTLN2 and 103 (4) NICCD patients in Japan (and other countries). From preliminary population analysis of the known nine SLC25A13 mutations, we found that the carrier frequency is high in China (1/79), Taiwan (1/98), and Korea (1/50) as well as Japan (1/69), suggesting that many patients with citrin deficiency exist in East Asia.